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Rahaba Marima,1 Mandisa Mbeje,1,2 Rodney Hull,1 Demetra Demetriou,1 Nompumelelo Mtshali,3 Zodwa Dlamini1 1SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria, South Africa; 2Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa; 3Department of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Zodwa Dlamini, Tel +27 12 319 2614, Email Zodwa.Dlamini@up.ac.zaAbstract: Prostate cancer (PCa) is a leading cause of mortality in men of African origin. While men of African descent in high-income countries (HICs) demonstrate poor prognosis compared to their European counterparts, African men on the African continent, particularly Southern Africa have shown even higher PCa mortality rates. Extrinsic factors such as the socioeconomic status, education level, income level, geographic location and race contribute to PCa patient outcome. These are further deepened by the African norms which are highly esteemed and may have detrimental effects on PCa patients’ health. Insights into African cultures and social constructs have been identified as key elements towards improving men’s health care seeking behaviour which will in turn improve PCa patients’ outcome. Compared to Southern Africa, the Eastern, Western and Central African regions have lower PCa incidence rates but higher mortality rates. The availability of cancer medical equipment has also been reported to be disproportionate in Africa, with most cancer resources in Northern and Southern Africa. Even within Southern Africa, cancer management resources are unevenly available where one country must access PCa specialised care in the neighbouring countries. While PCa seems to be better managed in HICs, steps towards effective PCa management are urgently needed in Africa, as this continent represents a significant portion of low–middle-income countries (LMICs). Replacing African men in Africa with African American men may not optimally resolve PCa challenges in Africa. Adopting western PCa management practices can be optimised by integrating improved core-African norms. The aim of this review is to discuss PCa disparities in Africa, deliberate on the significance of integrating African norms around masculinity and discuss challenges and opportunities towards effective PCa care in Africa, particularly in Southern Africa.Keywords: prostate cancer, PCa, Africa, disparities, low–middle-income countries, high-income countries, masculinity, African norms

Rodney Hull,1 Flavia Zita Francies,1 Meryl Oyomno,2 Zodwa Dlamini1,3 1SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa; 2Department of Surgery, Faculty of Health Sciences, Steve Biko Academic Hospital and the University of Pretoria, Pretoria 0007, South Africa; 3Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Parktown 2193, South AfricaCorrespondence: Zodwa DlaminiSA-MRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Room 4.35 Pathology Building, Hatfield 0028, South AfricaTel +27 761474878Email Zodwa.Dlamini@up.ac.zaAbstract: Each year, colorectal cancers (CRCs) affect over a quarter of a million people. The risk of developing CRC in industrialized nations is approximately 5%. When the disease is localised, treatment success rates range from 70– 90%; however, advanced CRC has a high mortality rate, consistently ranking in the top three causes of cancer-related deaths. There is a large geographic difference in global distribution, and CRC is predominantly associated with developed countries and a Western lifestyle and diet. As such, the developed world accounts for more than 63% of all cases of CRC. Geographic variations also predict cancer outcomes, which differ between racial and ethnic groups. This variation is due to inequalities in wealth, differences in the exposure to risk factors and barriers to high-quality cancer prevention, early detection and treatment. The aim of this paper was to review CRC in low- and middle-income countries such as South Africa, India, Brazil and China, and compare them with high-income countries such as the United States of America and the United Kingdom. It is important to note that these economically less developed countries, with historically low CRC rates, are experiencing an increased frequency of CRC. The review also discusses biological markers and genetic pathways involved in the development of colorectal cancer. Genes known to be responsible for the most common forms of inherited CRCs have also been identified but more remain to be identified. This would provide more candidate genes to be added to known biomarkers. CRC burden can be controlled through the widespread application of existing knowledge, such as reduced smoking habits, vaccination, early detection and promoting physical activity, accompanied by a healthy diet. An increased understanding of the molecular mechanisms and events underlying colorectal carcinogenesis will enable the development of new targets and therapeutic drugs.Keywords: colorectal cancer, WNT signaling pathway, RAS pathway, alcohol consumption, physical activity

Zodwa Dlamini, Rodney Hull, Tshepiso J Makhafola, Mzwandile MbeleSouth African Medical Research Council/University of Pretoria Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), Faculty of Health Sciences, University of Pretoria, Hatfield 0028, South AfricaCorrespondence: Zodwa DlaminiSouth African Medical Research Council/University of Pretoria Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), Faculty of Health Sciences, University of Pretoria, South AfricaTel +27 3 18 199 334/5Email Zodwa.dlamini@up.ac.zaAbstract: Obesity is the result of genetics which predisposes an individual to obesity and environmental factors, resulting in excessive weight gain. A well-established linear relationship exists between hypertension and obesity. The combined burden of hypertension and obesity poses significant health and economic challenges. Many environmental factors and genetic traits interact to contribute to obesity-linked hypertension. These include excess sodium re-absorption or secretion by the kidneys, a hypertensive shift of renal-pressure and activation of the sympathetic nervous system. Most individuals suffering from hypertension need drugs in order to treat their raised blood pressure, and while a number of antihypertensive therapeutic agents are currently available, 50% of cases remain uncontrolled. In order to develop new and effective therapeutic agents combating obesity-induced hypertension, a thorough understanding of the molecular events leading to adipogenesis is critical. With the advent of whole genome and exome sequencing techniques, new genes and variants which can be used as markers for obesity and hypertension are being identified. This review examines the role played by alternative splicing (AS) as a contributing factor to the metabolic regulation of obesity-induced hypertension. Splicing mutations constitute at least 14% of the disease-causing mutations, thus implicating polymorphisms that effect splicing as indicators of disease susceptibility. The unique transcripts resulting from the alternate splicing of mRNA encoding proteins that play a key role in contributing to obesity would be vital to gain a proper understanding of the genetic causes of obesity. A greater knowledge of the genetic basis for obesity-linked hypertension will assist in the development of appropriate diagnostic tests as well as the identification of new personalized therapeutic targets against obesity-induced hypertension.Keywords: obesity, hypertension, weight loss, angiogenesis, alternative splicing, gene regulation

Mohammed Alaouna,1 Rodney Hull,2 Clement Penny,1 Zodwa Dlamini2 1Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Research, Innovation & Engagements Portfolio, Mangosuthu University of Technology, Durban, South Africa Abstract: Esophageal cancer (EC) is an extremely aggressive cancer with one of the highest mortality rates. The cancer is generally only diagnosed at the later stages and has a poor 5-year survival rate due to the limited treatment options. China and South Africa are two countries with a very high prevalence rate of EC. EC rates in South Africa have been on the increase, and esophageal squamous cell carcinoma is the predominant subtype and a primary cause of cancer-related deaths in the black and male mixed ancestry populations in South Africa. The incidence of EC is highest in the Eastern Cape Province, especially in the rural areas such as the Transkei, where the consumption of foods contaminated with Fusarium verticillioides is thought to play a major contributing role to the incidence of EC. China is responsible for almost half of all new cases of EC globally. In China, the prevalence of EC varies greatly. However, the two main areas of high prevalence are the southern Taihang Mountain area (Linxian, Henan Province) and the north Jiangsu area. In both countries, environmental toxins play a major role in increasing the chance that an individual will develop EC. These associative factors include tobacco use, alcohol consumption, nutritional deficiencies and exposure to environmental toxins. However, genetic polymorphisms also play a role in predisposing individuals to EC. These include single-nucleotide polymorphisms that can be found in both protein-coding genes and in non-coding sequences such as miRNAs. The aim of this review is to summarize the contribution of genetic polymorphisms to EC in South Africa and to compare and contrast this to the genetic polymorphisms observed in EC in the most comprehensively studied population group, the Chinese. Keywords: esophageal squamous cell carcinoma, ESCC, adenocarcinoma, alcohol, smoking, diet, South Africa, China

Nonkululeko N Mthembu,1 Zukile Mbita,2 Rodney Hull,1 Zodwa Dlamini1 1Research, Innovation and Engagements, Mangosuthu University of Technology, Durban, 2Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, South Africa Abstract: Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. This aberrant splicing leads to abnormal production of protein and is caused by mutations in cis-acting elements or trans-acting factors in angiogenesis-related genes. Restoring the normal regulation of alternative splicing of angiogenic genes would alter the expression of protein isoforms and may confer normal cell physiology in patients with these cancers. This review highlights the abnormalities in alternative splicing of angiogenesis-related genes and their implication in HIV/AIDS-related cancers. This allows us to gain an insight into the pathogenesis of HIV/AIDS-related cancer and in turn elucidate the therapeutic potential of alternatively spliced genes in HIV/AIDS-related malignancies. Keywords: vascular endothelial growth factor, oncogenic viruses, hypoxia induced factor 1, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, therapies targeting alternative splicing

Zodwa Dlamini, Rodney Hull Research, Innovation & Engagements Portfolio, Mangosuthu University of Technology, Durban, South Africa Abstract: HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages of viral development, and this is achieved through the control of alternative splicing and the export of these transcripts from the nucleus. The nuclear export is controlled by the HIV protein Rev being required to transport incompletely spliced and partially spliced mRNA from the nucleus where they are normally retained. This implies a close relationship between the control of alternate splicing and the nuclear export of mRNA in the control of HIV-1 viral proliferation. This review discusses both the processes. The specificity and regulation of splicing in HIV-1 is controlled by the use of specific splice sites as well as exonic splicing enhancer and exonic splicing silencer sequences. The use of these silencer and enhancer sequences is dependent on the serine arginine family of proteins as well as the heterogeneous nuclear ribonucleoprotein family of proteins that bind to these sequences and increase or decrease splicing. Since alternative splicing is such a critical factor in viral development, it presents itself as a promising drug target. This review aims to discuss the inhibition of splicing, which would stall viral development, as an anti-HIV therapeutic strategy. In this review, the most recent knowledge of splicing in human immunodeficiency viral development and the latest therapeutic strategies targeting human immunodeficiency viral splicing are discussed. Keywords: alternative splicing, exonic splicing enhancer, exonic specific silencer, splicing based therapies, SR proteins, hnRNP, Rev, Tat, Vpr

Four types of resistive random access memory structures with an active layer comprising: (1) MoS2 (device A), (2) PVP (device B), (3) PVP and MoS2 bilayer (device C), and (4) PVP + MoS2 nanocomposites with 10 (device D), 20 (device E), 30 (device F) and 40 wt% (device G) MoS2, have been fabricated with Al and Ag as bottom and top electrodes, respectively. A study of resistive switching and electrical conduction mechanisms of these resistive random access memory modules revealed that devices A and B did not exhibit switching characteristics. Device C showed a combination of bipolar and threshold switching with a low switching voltage of 0:40 V. Device G portrayed bipolar switching at 0:56 V. In device C, space charge-limited conduction with a transition voltage Vtr = 0:24 V was observed, whereas in device G, Ohmic behaviour between 0.0 and 0.22 V, followed by trapping of charge in the 0.22-0.56 V regime before switching, was noticed. Both devices C and G showed a reasonable (≥ 10²) ON/OFF ratio. In nanocomposite devices, an increase in MoS2 content resulted in an increase in electrical conductivity in the Ohmic region, leading to threshold switching at 30 wt% (device F) and ultimately bipolar switching at 40 wt% (device G). These studies have shown that both switching and conduction mechanisms are sensitive to the type and composition of the active layer in the devices studied. [ABSTRACT FROM AUTHOR]

To accelerate the programme of infrastructure development and service provision, especially to the many previously disadvantaged South Africans, the government adopted the Public Private Partnership (PPP) approach in the late 1990s, as an intervention mechanism which was reflecting signs of success internationally. Sadly, over two decades later, the outcomes have been somewhat disappointing, especially where infrastructure development, upgrade, operation, maintenance and management is concerned across all three spheres of government as various PPP projects in the country take far longer than necessary to implement, some fail to reach the desired delivery or completion stage, while others are exposed to financial mismanagement, as well as outright corruption. This is evident in the number of incomplete and dilapidated transport infrastructure, incomplete and poorly maintained basic service infrastructure, the embezzlement and misappropriation of infrastructure funds, as well as the mounting infrastructure backlogs. The article collected data through a series of qualitative interviews with professionals in the PPP space with the aim of understanding the key factors that hamper PPP implementation efforts that must be addressed to improve future project outcomes. The article shows a notable degree of consensus among PPP professionals on the view that the PPP approach in its current form in South Africa is characterised by several weaknesses and gaps that make implementation efforts vulnerable to failure. [ABSTRACT FROM AUTHOR]

Back pain affects people across any socio-economic category and is a leading cause of absenteeism and decreased productivity in the workplace. This symptomatic condition is caused by multiple factors, making it difficult to manage. With a small proportion of people experiencing back pain due to pathological reasons, in the larger majority, back pain is due to a mechanical cause. Taking a complete history that includes identifying risk factors such as depression, poor posture, lack of exercise, older age and a physically demanding job is crucial to the effective management of the condition. Behavioural, psychological and social factors of the patient should form the backbone for treatment of back pain. Non-pharmacological management such as exercise and targeted physiotherapy should be the first-line treatment. However, if this provides poor results then pharmacological measures such as the use of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or muscle relaxants such as cyclobenzaprine should be considered. The pharmacist at the frontline can play a major role in assisting in the recovery of many patients. [ABSTRACT FROM AUTHOR]

Back pain affects people across any socio-economic category and is a leading cause of absenteeism and decreased productivity in the workplace. This symptomatic condition is caused by multiple factors, making it difficult to manage. With a small proportion of people experiencing back pain due to pathological reasons, in the larger majority, back pain is due to a mechanical cause. Taking a complete history that includes identifying risk factors such as depression, poor posture, lack of exercise, older age and a physically demanding job is crucial to the effective management of the condition. Behavioural, psychological and social factors of the patient should form the backbone for treatment of back pain. Non-pharmacological management such as exercise and targeted physiotherapy should be the first-line treatment. However, if this provides poor results then pharmacological measures such as the use of nonsteroidal antiinflammatory drugs (NSAIDs) like ibuprofen or muscle relaxants such as cyclobenzaprine should be considered. The pharmacist at the frontline can play a major role in assisting in the recovery of many patients. [ABSTRACT FROM AUTHOR]

In South Africa deaths related to colds and flu are at least three times higher when compared to the USA. The burden of HIV and tuberculosis in our country heightens the risk of severe flu-related illness. The common cold and flu are caused by very different viruses that share very similar symptoms. The common cold is a self-limiting upper respiratory tract viral infection and it is caused by the rhinovirus, coronavirus or the adenovirus. It usually resolves within 7-10 days. Flu is caused by the influenza virus and usually presents with headaches, myalgia, fever and body aches. There is no place for antibiotic usage in colds and flu management, and there is no clinical evidence which suggests that using antibiotics alters the course of the disease or prevents secondary infection. Treatment is mainly symptomatic and includes many over-the counter-medicines, specific antiviral agents and herbal treatment. [ABSTRACT FROM AUTHOR]

The study investigated the effects of probiotic bacteria (Lactobacillus reuteri ZJ625, Lactobacillus reuteri VB4, Lactobacillus salivarius ZJ614, and Streptococcus salivarius NBRC13956) administered as direct-fed microorganisms on growth performance and blood parameters of weaned piglets. Forty-five weaned piglets were divided into five treatments: antibiotic (PC), no antibiotic and no probiotic (NC), probiotic (P1), probiotic (P2), and combination of probiotics (P3). Fecal and ileum samples were collected for microbial count analysis. Blood samples were also collected from the animals at the end of the trial for the hematological and biochemical analysis and the ability of the probiotics to stimulate immunoglobulin G (IgG). Supplementation of probiotics had no effect on feed intake (FI). However, average daily weight gained (ADG) in the P3 treatment was higher than in other treatments and lowered the value of feed conversion ratio (FCR) of weaned piglets. Microbial count of fecal samples did not differ in all the treatments while ileum samples had lower enteric bacteria in P3 treatment when compared to other treatments. Concentration of albumin, globulin, neutrophils and basophils were higher in the NC treatment when compared to other treatment groups. The IgG concentration was highest in P3 compared to other treatments. Results suggested that probiotics have beneficial effects on growth performances, blood parameters, and IgG stimulation of weaned piglets. This advocates that probiotics will offer a significant benefit in pig farming by reducing the risk of post weaning diarrheal syndromes, and therefore enhance pig industry's economy. [ABSTRACT FROM AUTHOR]

Background/Objective: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. Methods: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. Results: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. Conclusions: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of Tulbaghia violacea , a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from T. violacea leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The T. violacea extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that T. violacea may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects.

Introduction: Workplace-based learning (WBL) is a method that combines theoretical knowledge with practical experience, promoting learner autonomy. Diagnostic radiography students in South Africa face challenges due to inconsistencies in clinical resources from the public and private sectors. Insufficient clinical resources can negatively impact students' competence and confidence in their skills. This study explored diagnostic radiography students' understanding of clinical resources., Methods: A qualitative exploratory-descriptive and contextual study with 21 participants at a single Higher Education institution (HEI) in South Africa was conducted through one-on-one semi-structured interviews on Microsoft Teams. The data collection tool was an interview guide. Students' narratives were transcribed and analysed using thematic analysis., Results: Thematic analysis revealed four themes: Theme one: Defining clinical resources in WBL; Theme two: Experiences with clinical resources in WBL; Theme three: Accessibility of clinical resources in WBL and Theme four: Defining clinical resources in WBL., Conclusion: Clinical resources are essential for radiography learning, promoting skills development and independent work. Balancing these resources with other activities is crucial for a comprehensive WBL experience. However, unequal access can hinder learning. Alternative solutions should be explored for specialised imaging techniques. Integrating simulation and collaborative practice between clinical practices and HEIs can enhance students' preparedness for real-world scenarios., (Copyright © 2024. Published by Elsevier Inc.)

RNA biology has revolutionized cancer understanding and treatment, especially in endocrine-related malignancies. This editorial highlights RNA's crucial role in cancer progression, emphasizing its influence on tumor heterogeneity and behavior. Processes like alternative splicing and noncoding RNA regulation shape cancer biology, with microRNAs, long noncoding RNAs, and circular RNAs orchestrating gene expression dynamics. Aberrant RNA signatures hold promise as diagnostic and prognostic biomarkers in endocrine-related cancers. Recent findings, such as aberrant PI3Kδ splice isoforms and epithelial-mesenchymal transition-related lncRNA signatures, unveil potential therapeutic targets for personalized treatments. Insights into m6A-associated lncRNA prognostic models and the function of lncRNA LINC00659 in gastric cancer represents ongoing research in this field. As understanding of RNA's role in cancer expands, personalized therapies offer transformative potential in managing endocrine-related malignancies. This signifies a significant stride towards precision oncology, fostering innovation for more effective cancer care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dlamini, Ladomery and Kahraman.)

In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients., Competing Interests: All the authors declare no conflict of interest., (© 2024 The Authors.)

Despite significant progress in the prevention, screening, diagnosis, prognosis, and therapy of breast cancer (BC), it remains a highly prevalent and life-threatening disease affecting millions worldwide. Molecular subtyping of BC is crucial for predictive and prognostic purposes due to the diverse clinical behaviors observed across various types. The molecular heterogeneity of BC poses uncertainties in its impact on diagnosis, prognosis, and treatment. Numerous studies have highlighted genetic and environmental differences between patients from different geographic regions, emphasizing the need for localized research. International studies have revealed that patients with African heritage are often diagnosed at a more advanced stage and exhibit poorer responses to treatment and lower survival rates. Despite these global findings, there is a dearth of in-depth studies focusing on communities in the African region. Early diagnosis and timely treatment are paramount to improving survival rates. In this context, radiogenomics emerges as a promising field within precision medicine. By associating genetic patterns with image attributes or features, radiogenomics has the potential to significantly improve early detection, prognosis, and diagnosis. It can provide valuable insights into potential treatment options and predict the likelihood of survival, progression, and relapse. Radiogenomics allows for visual features and genetic marker linkage that promises to eliminate the need for biopsy and sequencing. The application of radiogenomics not only contributes to advancing precision oncology and individualized patient treatment but also streamlines clinical workflows. This review aims to delve into the theoretical underpinnings of radiogenomics and explore its practical applications in the diagnosis, management, and treatment of BC and to put radiogenomics on a path towards fully integrated diagnostics.

Selenium is a trace and necessary micronutrient for human, animal, and microbial health. Many researchers have recently been interested in selenium nanoparticles (SeNPs) due to their biocompatibility, bioavailability, and low toxicity. As a result of their greater bioactivity, selenium nanoparticles are widely employed in a variety of biological applications. Physical, chemical, and biological approaches can all be used to synthesize selenium nanoparticles. Since it uses non-toxic solvents and operates at a suitable temperature, the biological technique is a preferable option. This review article addresses the processes implemented in the synthesis of SeNPs and highlights their medicinal uses, such as the treatment of fungi, bacteria, cancer, and wounds. Furthermore, we discuss the most recent findings on the potential of several biological materials for selenium nanoparticle production. The precursor, extract, process, time, temperature, and other synthesis criteria will be elaborated in conjunction with the product's physical properties (size, shape, and stability). The synergies of SeNP synthesis via various methods aid future researchers in precisely synthesizing SeNPs and using them in desired applications.

Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer "hallmarks". Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of ±2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsa-miR-4429 and hsa-miR-320b. This interaction in turn activates TGF-β-signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets.

Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed.

Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.

Colorectal cancer (CRC) ranks as one of the top causes of cancer mortality worldwide and its incidence is on the rise, particularly in low-middle-income countries (LMICs). There are several factors that contribute to the development and progression of CRC. Alternative splicing (AS) was found to be one of the molecular mechanisms underlying the development and progression of CRC. With the advent of genome/transcriptome sequencing and large patient databases, the broad role of aberrant AS in cancer development and progression has become clear. AS affects cancer initiation, proliferation, invasion, and migration. These splicing changes activate oncogenes or deactivate tumor suppressor genes by producing altered amounts of normally functional or new proteins with different, even opposing, functions. Thus, identifying and characterizing CRC-specific alternative splicing events and variants might help in designing new therapeutic splicing disrupter drugs. CRC-specific splicing events can be used as diagnostic and prognostic biomarkers. In this review, alternatively spliced events and their role in CRC development will be discussed. The paper also reviews recent research on alternatively spliced events that might be exploited as prognostic, diagnostic, and targeted therapeutic indicators. Of particular interest is the targeting of protein arginine methyltransferase (PMRT) isoforms for the development of new treatments and diagnostic tools. The potential challenges and limitations in translating these discoveries into clinical practice will also be addressed.

Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC.

Plants have demonstrated potential in providing various types of phytomedicines with chemopreventive properties that can combat prostate cancer. However, despite their promising in vitro activity, the incorporation of these phytochemicals into the market as anticancer agents has been hindered by their poor bioavailability, mainly due to their inadequate aqueous solubility, chemical instability, and unsatisfactory circulation time. To overcome these drawbacks, it has been suggested that the incorporation of phytochemicals as nanoparticles can offer a solution. The use of plant-based chemicals can also improve the biocompatibility of the formulated nanoparticles by avoiding the use of certain hazardous chemicals in the synthesis, leading to decreased toxicity in vivo. Moreover, in some cases, phytochemicals can act as targeting agents to tumour sites. This review will focus on and summarize the following points: the different types of nanoparticles that contain individual phytochemicals or plant extracts in their design with the aim of improving the bioavailability of the phytochemicals; the therapeutic evaluation of these nanoparticles against prostate cancer both in vitro and in vivo and the reported mode of action and the different types of anticancer experiments used; how the phytochemicals can also improve the targeting effects of these nanoparticles in some instances; and the potential toxicity of these nanoparticles.

Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are modeled after those of papillary thyroid carcinoma (PTC), even though FTC is more aggressive. FTC has a greater propensity for haematogenous metastasis than PTC. Furthermore, FTC is a phenotypically and genotypically heterogeneous disease. The diagnosis and identification of markers of an aggressive FTC depend on the expertise and thoroughness of pathologists during histopathological analysis. An untreated or metastatic FTC is likely to de-differentiate and become poorly differentiated or undifferentiated and resistant to standard treatment. While thyroid lobectomy is adequate for the treatment of selected patients who have low-risk FTC, it is not advisable for patients whose tumor is larger than 4 cm in diameter or has extensive extra-thyroidal extension. Lobectomy is also not adequate for tumors that have aggressive mutations. Although the prognosis for over 80% of PTC and FTC is good, nearly 20% of the tumors behave aggressively. The introduction of radiomics, pathomics, genomics, transcriptomics, metabolomics, and liquid biopsy have led to improvements in the understanding of tumorigenesis, progression, treatment response, and prognostication of thyroid cancer. The article reviews the challenges that are encountered during the diagnostic work-up, staging, risk stratification, management, and follow-up of patients who have FTC. How the application of multi-omics can strengthen decision-making during the management of follicular carcinoma is also discussed.

Angiogenesis, the generation of new blood vessels, is one of the hallmarks of cancer. The growing tumor requires nutrients and oxygen. Recent evidence has shown that tumors release signals to attract new nerve fibers and stimulate the growth of new nerve fibers. Neurogenesis, neural extension, and axonogenesis assist in the migration of cancer cells. Cancer cells can use both blood vessels and nerve fibers as routes for cells to move along. In this way, neurogenesis and angiogenesis both contribute to cancer metastasis. As a result, tumor-induced neurogenesis joins angiogenesis and immunosuppression as aberrant processes that are exacerbated within the tumor microenvironment. The relationship between these processes contributes to cancer development and progression. The interplay between these systems is brought about by cytokines, neurotransmitters, and neuromodulators, which activate signaling pathways that are common to angiogenesis and the nervous tissue. These include the AKT signaling pathways, the MAPK pathway, and the Ras signaling pathway. These processes also both require the remodeling of tissues. The interplay of these processes in cancer provides the opportunity to develop novel therapies that can be used to target these processes.

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla . Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna ) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla . CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)